CAJ | 학술논문

目的：对肥胖儿童中黑皮素4受体（MC4R）基因编码区进行突变位点筛查，研究其与肥胖相关指标的关系，并对突变可能造成的基因功能改变进行预测。方法选择北京市160例7~18岁重度肥胖和100例体重正常的儿童青少年，进行身体测量和血生化指标检测。使用PCR、单链构象多态性和测序方法进行MC4R基因编码区筛查。使用生物信息学网络数据库对筛出的突变进行功能预测。结果肥胖儿童中筛出杂合子错义突变3例（Val95Ile、Val166Ile、Val179Ala）；在对照组中筛出杂合子错义突变1例（Met218Thr）；Val103Ile变异在肥胖组和对照组中分别有7例（4.4％）和6例（6.0％）（P>0.05）。其中肥胖组中筛出的Val179Ala为首次发现的杂合子突变。携带Val95Ile、Val166Ile或Val179Ala突变的3例肥胖儿童与未携带这3个突变的其他157例肥胖儿童的BMI、体重、腰围、臀围、血脂指标、血糖和脂肪百分比的比较差异均无统计学意义（P>0.05）。对筛出的突变进行功能预测，发现上述5个变异均可能对蛋白质功能产生影响。结论在肥胖儿童MC4R基因编码区共发现5个变异，其中Val179Ala为首次发现的新突变；功能预测发现这5个变异均可能对蛋白质的功能造成影响。
목적：대비반인동중흑피소4수체（MC4R）기인편마구진행돌변위점사사，연구기여비반상관지표적관계，병대돌변가능조성적기인공능개변진행예측。방법선택북경시160례7~18세중도비반화100례체중정상적인동청소년，진행신체측량화혈생화지표검측。사용PCR、단련구상다태성화측서방법진행MC4R기인편마구사사。사용생물신식학망락수거고대사출적돌변진행공능예측。결과비반인동중사출잡합자착의돌변3례（Val95Ile、Val166Ile、Val179Ala）；재대조조중사출잡합자착의돌변1례（Met218Thr）；Val103Ile변이재비반조화대조조중분별유7례（4.4％）화6례（6.0％）（P>0.05）。기중비반조중사출적Val179Ala위수차발현적잡합자돌변。휴대Val95Ile、Val166Ile혹Val179Ala돌변적3례비반인동여미휴대저3개돌변적기타157례비반인동적BMI、체중、요위、둔위、혈지지표、혈당화지방백분비적비교차이균무통계학의의（P>0.05）。대사출적돌변진행공능예측，발현상술5개변이균가능대단백질공능산생영향。결론재비반인동MC4R기인편마구공발현5개변이，기중Val179Ala위수차발현적신돌변；공능예측발현저5개변이균가능대단백질적공능조성영향。
ObjectiveTo screen the coding region of melanocortin-4 receptor gene (MC4R) for mutations in children, analyze the association of the identified variants with obesity-related phenotypes, and predict the potential functions of the identified variants.MethodsA case-control study was conducted in 160 severely obese children and 100 normal-weight controls, all aged 7-18 years. Their anthropometric data were collected and blood tests were performed. The coding region of MC4R gene was screened by polymerase chain reaction (PCR), single strand conformation polymorphism and sequencing, and the potential functions of the identiifed variants were predicted by related online databases.ResultsThree heterozygous missense mutations were identiifed in obese children (Val95Ile, Val166Ile and Val179Ala), and one heterozygous missense mutation was found in controls (Met218Thr). Val103Ile variant was found to be carried by seven subjects in the obese group and six in the control group (P>0.05). Val179Ala was a newly identified heterozygous mutation. No significant differences in BMI, weight, waist circumstance, hip circumstance, serum lipid parameters, fasting glucose, and body fat percentage were found between Val95Ile, Val166Ile or Val179Ala mutation carriers and non-carriers in obese children. The function prediction of the variants showed that all the ifve identiifed variants inlfuenced the protein function.ConclusionsFive variants were identiifed in the coding region of MC4R gene, among which Val179Ala was newly identiifed. All the ifve variants might inlfuence the protein function as evidenced by online prediction.